Biomedical subjects

Barbara P Rattner

Publications and source records attributed to Barbara P Rattner.

4 recordsLinked to original sources

PubMed2005

The severity of roX1 mutations is predicted by MSL localization on the X chromosome.

Dosage compensation equalizes the expression of sex-linked genes between males and females. Most genes on the X chromosome of male Drosophila are transcribed at an increased level, contributing to compensation. The roX1 and roX2 genes produce non-coding transcripts that localize along the X-chromosome of male flies. Although lacking sequence similarity, they are necessary but redundant components of a system that up-regulates gene expression. Simultaneous mutation of both roX genes disrupts the X-limited distribution of proteins that modify chromatin to enhance gene expression. We have generated and characterized loss of function roX1 alleles that display a continuum of activity. Those that support intermediate male survival have strikingly reduced RNA accumulation, while alleles with minor contributions to male viability typically lack detectable transcript accumulation. Severely mutated roX1 alleles retain some ability to direct modifying proteins to the X chromosome. This ability predicts the level of male survival that each allele supports. This points to a peripheral or transient role for roX in the RNA and protein complex that binds to and regulates the X chromosome.

Alleles↗

PubMed2004

Worm chromosomes call for recognition!

Many organisms face a dilemma rooted in the unequal numbers of X chromosomes carried by the two sexes and the need to maintain equivalent expression of X-linked genes. Several strategies have arisen to cope with this problem. All rely on accurately targeting epigenetic modifications to entire chromosomes. Targeting results from the action of recognition elements that attract modification and may rely on spreading of modification in cis along the affected chromosome. A recent report describing the first X chromosome recognition element from C. elegans opens the way to defining the relative contributions of these factors to the compensation of X-linked gene expression in worms.1 Extrachromosomal arrays composed of a C. elegans recognition element attract proteins that modify the C. elegans X chromosomes and interact genetically with mutations disrupting compensation. Moreover, examination of X:A translocations provides the first evidence for spreading of modification along C. elegans X chromosomes.

Animals↗

PubMed2004

Drosophila male-specific lethal 2 protein controls sex-specific expression of the roX genes.

The MSL complex of Drosophila upregulates transcription of the male X chromosome, equalizing male and female X-linked gene expression. Five male-specific lethal proteins and at least one of the two noncoding roX RNAs are essential for this process. The roX RNAs are required for the localization of MSL complexes to the X chromosome. Although the mechanisms directing targeting remain speculative, the ratio of MSL protein to roX RNA influences localization of the complex. We examine the transcriptional regulation of the roX genes and show that MSL2 controls male-specific roX expression in the absence of any other MSL protein. We propose that this mechanism maintains a stable MSL/roX ratio that is favorable for localization of the complex to the X chromosome.

Animals↗

PubMed2002

The roX genes encode redundant male-specific lethal transcripts required for targeting of the MSL complex.

The roX1 and roX2 genes of Drosophila produce male-specific non-coding RNAs that co-localize with the Male-Specific Lethal (MSL) protein complex. This complex mediates up-regulation of the male X chromosome by increasing histone H4 acetylation, thus contributing to the equalization of X-linked gene expression between the sexes. Both roX genes overlap two of approximately 35 chromatin entry sites, DNA sequences proposed to act in cis to direct the MSL complex to the X chromosome. Although dosage compensation is essential in males, an intact roX1 gene is not required by either sex. We have generated flies lacking roX2 and find that this gene is also non-essential. However, simultaneous removal of both roX RNAs causes a striking male-specific reduction in viability accompanied by relocation of the MSL proteins and acetylated histone H4 from the X chromosome to autosomal sites and heterochromatin. Males can be rescued by roX cDNAs from autosomal transgenes, demonstrating the genetic separation of the chromatin entry and RNA-encoding functions. Therefore, the roX1 and roX2 genes produce redundant, male-specific lethal transcripts required for targeting the MSL complex.

Acetyltransferases↗